Studies with both prokaryotic and eukaryotic cells suggest that the mutagenic activities of an organic compound can be used to test for and predict its carcinogenicity. It is proposed that S49 mouse lymphoma tissue culture cells be used as the target for mutation induction in a carcinogen screening system. Multiple genetic markers have been studied in these cells. Mutants resistant to dibutyryl cyclic AMP, dexamethasone, 6-thioguanine or ouabain are well-suited for quantitative analysis of induction. These agents select, respectively, cells with defects in cyclic AMP-dependent protein kinase, glucocorticoid receptor, hypoxanthine-guanine phosphoribosyltransferase and ouabain-sensitive Na ion/K ion-ATPase. Beginning with aflatoxin B1 and benzo(a)pyrene, S49 cells will be incubated with carcinogens and, after a suitable expression time, cloned in agar with each of the selective media to determine the frequency of induced mutation for each marker. Because many compounds become active only after metabolic conversion, liver microsomal fractions will be added to the incubation mixture as a source of mixed function oxidases. By extending this analysis to a large number of compounds, the sensitivity and efficacy of each marker for carcinogen testing will be determined. The use of multiple markers may make it possible to infer plausible mechanisms of carcinogen action.